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Asger Sonne,1 Jesper B Andersen,2 Lars S Rasmussen11Department of Anaesthesia, Centre of Head and Orthopaedics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 2Department of Neurosurgery, The Neuroscience Centre, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkIntroduction: Spontaneous (non-traumatic) subarachnoid hemorrhage (ntSAH) is frequently suspected in the emergency department, but the incidence rate is low. Diagnosis registers can provide valuable data for research in uncommon conditions like ntSAH. Unfortunately, validity vary in the registers. We aimed to assess the validity of the ntSAH diagnosis in the Danish National Patient Register (DNPR) and secondly to describe patients misclassified as ntSAH and to calculate the incidence rate of ntSAH.Methods: From the DNPR we extracted information on patients at least 18 years of age on admission registered with a diagnosis of ntSAH and admitted to a hospital in the Capital Region of Denmark between January 1, 2008 and December 31, 2014. Two independent investigators reviewed the medical records to assess if the diagnosis could be confirmed. Those not confirmed were categorized according to a predeveloped case report form.Results: We identified 1101 patients with a diagnosis of ntSAH; medical records were accessible for 1069 (97.7%) and 842 (78.8%) met the inclusion criteria. The diagnosis was confirmed in 537 patients (63.8% (95% confidence interval: 60.5–67.0%)). Among patients where ntSAH was not confirmed, 122 (40.0%) had a traumatic subarachnoid hemorrhage (tSAH), ntSAH had been suspected in 57 (18.9%) patients but was not substantiated during admission, while parenchymal hemorrhages were identified in 45 (14.5%) patients. The incidence rate was 5.5 (95% CI: 4.9–6.1) per 100,000 persons per year.Conclusion: We found a positive predictive value (PPV) of 63.8% for the diagnosis of non-traumatic subarachnoid hemorrhage in the Danish National Patient Register. The low PPV suggests that care should be taken if unvalidated data are used for research and that results of previous studies should be interpreted with caution.Keywords: subarachnoid hemorrhage, diagnosis register, diagnosis validation, incidence rate, non-traumatic, Danish National Patient Register

Tea is one of the worlds most popular and widely consumed beverages. It is a common pastime to enjoy a cup of tea in the sunshine. However, little attention has been given to understanding the possible photochemical reactions occurring beneath the calm surface of brewed tea. Epigallocatechin gallate (EGCG), which is widely used in food and beverages, is the most significant active ingredient found in tea. In this study, we investigated the presence of free radicals in both an aqueous EGCG solution and brewed tea under simulated sunlight conditions. To our surprise, we unexpectedly observed the production of hydroxyl radicals (•OH) in brewed tea. It was found that sunlight irradiation played a critical role in the formation of •OH, independent of the presence of metal ions. Furthermore, we demonstrated that the •OH generated from the EGCG aqueous solution induced cell cytotoxicity and DNA damage in vitro. Considering the crucial role of •OH in various fields, including human health and the environment, it is important to further explore the practical implications of •OH production in brewed tea under sunlight. In summary, our study unveils the unexpected formation of •OH in brewed tea and emphasizes the significance of sunlight-induced reactions. The observed cytotoxic and DNA-damaging effects of •OH emphasize the importance of understanding the potential health consequences associated with tea consumption. Further research in this area will contribute to a better understanding of the broader implications of •OH production in brewed tea under sunlight.

Summary: Background/aims: During the first outbreak of COVID-19 knowledge regarding nutritional status and target areas of the nutritional treatment to patients admitted to the hospitals with COVID-19 was limited. Therefore, the aim was 1) to describe baseline characteristics including nutritional status, nutritional risk, energy- and protein intake, nutritional route, and Nutrition Impact Symptoms (NIS) known to have an impact on the nutritional intake; 2) to compare these characteristics in patients who, respectively, survived or died within 30 days after discharge and 3) to describe nutritional aspects in the transition between hospitalisation and a home setting. Methods: This was an observational study. Patients admitted with COVID-19 in 2020 and referred to clinical dietitians were enrolled. Data on nutritional status, nutritional risk, NIS, nutritional treatment, grade of inflammation, 30-days mortality and readmissions rate and nutritional aspects after discharge were collected from the patient journal. Results: We included 81 patients, 41 (51%) male, median age 75 (IQR: 63–83). Patients were referred to the clinical dietitians at median day 4 (IQR: 3–8) of the hospital stay. The median BMI was 25 (IQR: 21–28) and 58 (83%) were at nutritional risk. Nutrition route was primarily oral (89%). The three most common NIS were; decreased appetite (88%), shortness of breath (55%), and early satiety (47%).At the 30 days follow-up 23 (28%) patients were deceased, of these 16 (70%) before discharge. The patients who died were older (median 82 vs. 72 y, P=0.002), and more were admitted from a care facility (48 vs. 17%, P=0.005). Further, among those who died fewer covered their energy requirement (25 vs. 43%, P=0.001), and protein requirement (23 vs. 34%, P=0.032). Also chewing- and swallowing problems were more prevalent in those who died (45 vs. 17%, P=0.048). There were no differences in nutritional status, nutritional risk, or nutritional route among the two groups. A total of 21 (26%) patients were readmitted within 30 days.At discharge only 11 (14%) patients had a nutritional discharge plan made by the clinical dietician. Up to one fifth still experienced NIS with early satiety (20%), chewing or swallowing problems (15%) and respiratory problems (15%) being the most frequent. Conclusions: Hospitalized patients with COVID-19 had several NIS, a high prevalence of nutritional risk and the majority had a nutritional intake below requirement. The mortality was high, especially during hospitalisation, and those patients that died had a lower intake of energy and protein and hence also coverage of requirement. Most patients were fed orally during hospitalisation. More than one fourth of the patients were readmitted within 30 days. Few patients had a nutritional discharge plan made by the dietitian and up till one fifth of the patients still suffered from NIS.Therefore, nutritional treatment is relevant in this group of patients.

Intelligent chatbots powered by large language models (LLMs) have recently been sweeping the world, with potential for a wide variety of industrial applications. Global frontier technology companies are feverishly participating in LLM-powered chatbot design and development, providing several alternatives beyond the famous ChatGPT. However, training, fine-tuning, and updating such intelligent chatbots consume substantial amounts of electricity, resulting in significant carbon emissions. The research and development of all intelligent LLMs and software, hardware manufacturing (e.g., graphics processing units and supercomputers), related data/operations management, and material recycling supporting chatbot services are associated with carbon emissions to varying extents. Attention should therefore be paid to the entire life-cycle energy and carbon footprints of LLM-powered intelligent chatbots in both the present and future in order to mitigate their climate change impact. In this work, we clarify and highlight the energy consumption and carbon emission implications of eight main phases throughout the life cycle of the development of such intelligent chatbots. Based on a life-cycle and interaction analysis of these phases, we propose a system-level solution with three strategic pathways to optimize the management of this industry and mitigate the related footprints. While anticipating the enormous potential of this advanced technology and its products, we make an appeal for a rethinking of the mitigation pathways and strategies of the life-cycle energy usage and carbon emissions of the LLM-powered intelligent chatbot industry and a reshaping of their energy and environmental implications at this early stage of development.

Abstract Gestational diabetes mellitus (GDM) adversely affects offspring glucose homeostasis and risk of developing obesity. Here, we examined the association between glycemia in pregnant women with overweight or obesity without GDM and offspring metabolic health. Maternal fasting glucose concentrations and glucose 2-h after an oral glucose tolerance test (OGTT) were measured in 208 women with a pre-pregnancy body mass index (BMI) of 28–45 kg/m2 without GDM. Offspring outcomes were collected at birth, 3, and 5 years of age. Linear mixed models with time as fixed factor and subject ID as random effects were used for analysis. No associations were found between maternal fasting or 2-h glucose concentrations with offspring glucose and insulin concentrations from birth to 5 years of age. However, maternal fasting glucose in GW 28 and 36, and 2-h OGTT glucose in GW 28 were positively associated with C-peptide concentration at birth. Maternal fasting glucose concentrations in GW 28 and 36 were positively associated with weight-for-length, and maternal fasting glucose in GW 36 was associated with BMI z-score at birth. In summary, blood glucose in pregnant women with overweight or obesity is positively associated with offspring C-peptide concentration, weight-for-length, and BMI z-score at birth, even in the absence of GDM.

The objective was to identify the main factors influencing micronutrient policies in the opinion of policy actors in ten European countries. Study was carried out during Jan-Nov 2010 in European countries: the Czech Republic, Denmark, England, Germany, Greece, Italy, the Netherlands, Norway, Poland and Spain. Semi-structured qualitative interviews were conducted with representatives of stakeholders involved in the vitamin D, folate and iodine policy making process. Fifty eight key informants representing mainly scientific advisory bodies (n=24) and governmental organisations (n=19) participated in the study. The remaining interviewees represented non-governmental organisations (n=6), industry (n=4) or were independent academic or health professional experts (n=5). Data were analysed by theoretical interpretative thematic analysis. Insights from interviewees on the development of micronutrient policies were grouped using the Public Health Nutrition Policy-making model. The main factors influencing the micronutrient policies were: systematic monitoring of nutrition and health, causal relationships between consumers’ diet-related behaviours and health outcomes, scientific recommendations from national bodies (Science area); scientific recommendations from international authorities and experiences of other countries, EU legislation, cultural factors (Wider context) and political environment, national capacity to deal with the problem, national legislation, economics, stakeholder engagement, relationships between stakeholders (Policy and institutions area). The spectrum and weight of the factors influencing nutritional policy depends on nutrient, country and degree of its “advanced status” within nutrition policy, political environment, culture and socio-economic conditions as well as the point of view (who is expressing the opinion).

The humpback whale (Megaptera novaeangliae) is a mysticete with a cosmopolitan distribution, including Brazil (1). Morbillivirus in cetaceans first occurred in 1988 in Europe. Since then, various strains of cetacean [...]

Abstract Biochar, a carbon-rich material produced from biomass waste through thermal conversion, holds great environmental promise. This article offers a comprehensive overview of the various feedstocks used in biochar production, the different types of thermal degradation processes, biochar characterization, properties, modifications to engineered materials, and their applications in the environment. The quality of biochar, including surface area, pore size and volume, and functional group formation, is significantly influenced by the specific conditions under which thermal conversion takes place. Each of the diverse processes employed to produce biochar yields a distinct set of properties in the final product. In recent years, biochar has gained widespread recognition and utilization in diverse fields such as wastewater treatment, carbon sequestration, reduction of greenhouse gas emissions, biogas production, catalysis in biofuel industries, construction, and soil enhancement. In summary, biochar is a promising environmental mitigation tool to achieve a sustainable environment. In addition to its benefits, the application of biochar presents several challenges, including the selection of feedstocks, methods of biochar production, modifications to biochar, the properties of biochar, and the specific applications of biochar. The current review summarizes factors that could lead to significant advancements in future applications. Graphical Abstract

ABSTRACT A dermoid is the presence of normal skin in an abnormal place. A mixed-breed, male, 4-month-old cat was presented with a history of ocular discomfort in the right eye. Ophthalmic examination on the right eye revealed lacrimation, blepharospasm, ocular discomfort and mild conjunctival hyperaemia. A mass with hair with a diameter of 5 mm on the temporal part of the bulbar conjunctiva was observed. Surgical excision of the mass was recommended. Histopathology of the excised tissue confirmed the diagnosis of a dermoid. There was no evidence of lesion recurrence 12 months after surgery. In the present case, complete surgical excision of the dermoid was curative. Although rare, dermoid should be included in the differential diagnosis of conjunctival disorders in cats.

Cetacean morbillivirus is an etiologic agent associated with strandings of live and dead cetacean species occurring sporadically or as epizootics worldwide. We report 2 cases of cetacean morbillivirus in humpback whales (Megaptera novaeangliae) in Brazil and describe the anatomopathological, immunohistochemical, and molecular characterization findings in the specimens.

Abstract The oral cavity harbors complex communities comprising bacteria, archaea, fungi, protozoa, and viruses. The oral microbiota is establish at birth and develops further during childhood, with early life factors such as birth mode, feeding practices, and oral hygiene, reported to influence this development and the susceptibility to caries. We here analyzed the oral bacterial composition in saliva of 260 Swedish children at two, three and five years of age using 16S rRNA gene profiling to examine its relation to environmental factors and caries development at five years of age. We were able to assign the salivary bacterial community in each child at each time point to one of seven distinct clusters. We observed an individual dynamic in the development of the oral microbiota related to early life factors, such as being first born, born by C-section, maternal perinatal antibiotics use, with a distinct transition between three and five years of age. Different bacterial signatures depending on age were related to increased caries risk, while Peptococcus consistently linked to reduced risk of caries development.

Objective To assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple injections of M6495, a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS‐5) nanobody, in healthy volunteers and patients with osteoarthritis. Methods Two randomized, placebo‐controlled, double‐blind studies were performed. Study 1 enrolled 54 healthy male volunteers who received one subcutaneous (s.c.) injection of M6495 (1‐300 mg) or placebo (ratio 2:1), evaluating safety, PK, and PD as changes in the serum aggrecan fragment alanine‐arginine‐glycine‐serine (ARGS). Study 2 enrolled 32 patients with osteoarthritis with Kellgren–Lawrence grades 2 to 4 and pain greater than or equal to 40 on the Western Ontario and McMaster Universities Arthritis Index pain subscale at screening and evaluated the safety, PK, and PD of three doses every two weeks (75‐300 mg per dose) or six once‐weekly M6495 s.c. doses (300 mg) or placebo (ratio 3:1) over 106 days’ follow‐up. Results M6495 in single and multiple doses of less than or equal to 300 mg s.c. weekly was well tolerated with no clinically significant changes in any safety parameter. Adverse events more frequently reported in the M6495 groups were mostly mild cases of injection site reactions, myalgia, and nausea, which resolved after treatment cessation. The elimination half‐life of single s.c. doses of M6495 ranged from 79 to 267 hours. M6495 administration substantially reduced serum ARGS levels, indicative of target engagement and indicating disease‐modifying potential of M6495. Conclusion Treatment with M6495 in single and multiple doses up to and including 300 mg s.c. was found to be well tolerated and adequately safe for further clinical evaluation of potential disease‐modifying effects.

Neural stem cells (NSCs) are considered to be valuable candidates for delivering a variety of anti‐cancer agents, including oncolytic viruses, to brain tumors. However, owing to the previously reported tumorigenic potential of NSC cell lines after intranasal administration (INA), here we identified the human hepatic stellate cell line LX‐2 as a cell type capable of longer resistance to replication of oncolytic adenoviruses (OAVs) as a therapeutic cargo, and that is non‐tumorigenic after INA. Our data show that LX‐2 cells can longer withstand the OAV XVir‐N‐31 replication and oncolysis than NSCs. By selecting the highly migratory cell population out of LX‐2, an offspring cell line with a higher and more stable capability to migrate was generated. Additionally, as a safety backup, we applied genomic herpes simplex virus thymidine kinase (HSV‐TK) integration into LX‐2, leading to high vulnerability to ganciclovir (GCV). Histopathological analyses confirmed the absence of neoplasia in the respiratory tracts and brains of immuno‐compromised mice 3 months after INA of LX‐2 cells. Our data suggest that LX‐2 is a novel, robust, and safe cell line for delivering anti‐cancer and other therapeutic agents to the brain.